Urantide is a selective and competitive urotensin-II (UT) receptor antagonist, with the pKB value of 8.32 [1]. Urantide can down-regulate the expression levels of UT and GPR14 in the liver and reduce the phosphorylation levels of Erk1/2 and JNK to prevent hepatic steatosis [2]. Urantide has been widely used to regulate the contraction and calcium release in the thoracic aorta of rats[3].
In vitro, Urantide (1μM) treatment for 48 hours significantly inhibited the urotensin II-stimulated proliferation of rat vascular smooth muscle cells (VSMCs) and induced cell cycle arrest[4]. Treatment with 1μM Urantide for 48 hours significantly reduced the expression of p-JAK2 and p-STAT3 proteins and the phenotypic transformation in rat VSMCs [5].
In vivo, Urantide treatment via intraperitoneal injection at a dose of 30μg/kg three times within 2 weeks significantly alleviated myocardial injury in rats with atherosclerosis[6]. Intraperitoneal injection of 10μg/kg/day dose of Urantide for 3 weeks significantly alleviated the increase in pulmonary arterial hypertension (PAH) induced by monocrotaline in rats and improved the structure and function of the right ventricle[7].
References:
[1] Carotenuto A, Auriemma L, Merlino F, et al. Lead optimization of P5U and urantide: discovery of novel potent ligands at the urotensin-II receptor[J]. Journal of Medicinal Chemistry, 2014, 57(14): 5965-5974.
[2] Cui H, Lin Y, Xie L, et al. Urantide decreases hepatic steatosis in rats with experimental atherosclerosis via the MAPK/Erk/JNK pathway[J]. Molecular Medicine Reports, 2021, 23(4): 1-10.
[3] Camarda V, Song W, Marzola E, et al. Urantide mimics urotensin-II induced calcium release in cells expressing recombinant UT receptors[J]. European journal of pharmacology, 2004, 498(1-3): 83-86.
[4] Zhao J, Zhang S F, Shi Y, et al. Effects of urotensin II and its specific receptor antagonist urantide on rat vascular smooth muscle cells[J]. Bosnian Journal of Basic Medical Sciences, 2013, 13(2): 78.
[5] Wang T, Xie L, Bi H, et al. Urantide alleviates the symptoms of atherosclerotic rats in vivo and in vitro models through the JAK2/STAT3 signaling pathway[J]. European Journal of Pharmacology, 2021, 902: 174037.
[6] Zhao J, Miao G, Wang T, et al. Urantide attenuates myocardial damage in atherosclerotic rats by regulating the MAPK signalling pathway[J]. Life sciences, 2020, 262: 118551.
[7] Wang Y, Tian W, Xiu C, et al. Urantide improves the structure and function of right ventricle as determined by echocardiography in monocrotaline-induced pulmonary hypertension rat model[J]. Clinical rheumatology, 2019, 38(1): 29-35.